Through a large-scale sequencing of genomic DNA at 3p22-->p21.3, we have isolated two human genes (ORCTL3 alias OCTL1 and ORCTL4 alias OCTL2) encoding novel members of the family of organic-cation transporter molecules. The predicted proteins revealed the highest similarities to recently- isolated organic-cation transporter proteins, rat OCT-1r, rat NLT and mouse NKT. The transcripts of both genes were expressed ubiquitously in various human tissues, but some tissue-specific transcripts were also observed in kidney, testis, or skeletal muscle. The two genes are clustered within a 52-kb region of genomic DNA and ORCTL4 lies about 27 kb telomeric to ORCTL3 in the genomic DNA sequence in a tail-to-head orientation.